The research proposed in this application is designed to purify and characterize an inihibitor of aortic endothelial cell proliferation which we have isolated from embryonic, newborn and adult bovine vitreous and from adult human vitreous. The inhibitor will be purified by column chromatographic and isoelectrofocusing techniques. The bovine vitreous inhibitor will be compared with that obtained from normal and diabetic human vitreous and with that secreted into the medium by calf vitreous hyalocytes. It has been proposed that a cartilage inhibitor of endothelial cell growth is a protease inhibitor. Vitreous also contains protease inhibitors and we will determine whether the vitreous protease inhibitory and endothelial cell growth inhibitory activities are properties of the same component. The vitreous inhibitor may be of importance in the regression of the hyaloid vascular system during late embryonic development an in the maintenance of the vitreous as a clear, vessel-free tissue. An imbalance between the vitreous inhibitor and an angiogenesis stimulator we have found to be released from necrotic and/or hypoxic retina may play a role in the abnormal proliferation of blood vessels into the vitreous seen in diabetic retinopathy. It is also known that implantation of tumors into the vitreous results in tumor dormancy without the tumor-induced neovascularization which normally nourishes a growing tumor. The vitreous inhibitor will be tested to determine whether it inhibits tumor angiogenesis factor (TAF) stimulation of vascular endothelial cell proliferation. TAF will be purified from the Walker 256 rat tumor by recently developed techniques.